The red cell membrane is often used as a model of other biological membranes, since i) it is abundantly available in highly purified form, ii) it can be obtained from humans without harming the donor, iii) its structure is comparatively simple, iv) the major components are found in virtually all animal cell plasma membranes, and v) pathological lesions arising in other cell membranes are often manifested in the red cell (e.g. diabetes, muscular dystrophy, etc.). For this reason, a thorough understanding of the structure and regulation of the red cell membrane may be a logical stepping stone to unraveling the molecular bases of health problems affecting other cell membranes. We are seeking to elucidate the structure, regulation, biological functions, and pathological states of interactions involving the major membrane protein, termed band 3. Specifically we intend to i) examine the regulation of the association of band 3 with ankyrin (the major linkage between the cytoskeleton and the membrane), ii) characterize the interaction between band 3 and band 4.1, a second major cytoskeletal protein, iii) study the regulation of membrane- cytoskeletal interactions during cell swelling and shrinking, and iv) confirm our mechanisms which explains how the body distinguishes old from young red cells and selectively destroys the former. Research on this letter topic may provide clues for extending the life of stored blood. Research on the former projects should aid in understanding and eventually treating such diseases as sickle cell anemia, hereditary spherocytosis, hereditary elliptocytosis, and hereditary pyropoikilocytosis, as well as maladies of nonerythroid cells. Methods used to investigate the above issues involve predominately protein chemistry, with contributions from immunology and molecular biology.